The aim of this research program involves elucidation of the ion permeability and signal transduction mechanisms expressed by cells cultured from the embryonic and early postnatal mammalian CNS or the adult endocrine pituitary, and by cultured fibroblasts transfected with exogenous genes encoding specific transmitter receptors and second-messenger molecules. The experiments are carried out on single cells or pairs of cells using patch-type electrical recordings and microspectrophotometric analyses of indicator-dye signals. Major findings include: 1) hippocampal GABergic neurons transmit inhibitory signals at pre- and postsynaptic sites, with the former acting to depress post-synaptic signals in all-or-none and graded ways through actions at GABA A and GABA B receptors on pre-synaptic terminals; 2) GABA-activated Cl-conductance is depressed by cellular depolarization in a Co2+- sensitive manner; 3) hippocampal cell bodies have three additional Cl- channels gated by voltage and/or Ca2+; 4) depresses NMDA- activated cation flux, depolarization-triggered Ca2+ conductance and voltage-gated transient and sustained K+ conductances; 4) maganin-2, a naturally occurring antibiotic and anti-tumor peptide, forms Cl-ion channels in lipid bilayers and irreversibly disrupts electrical recordings from pituitary tumor cells in a Cl- ion dependent way; 6) pertussis toxin blocks all effects of somatostatin on membrane excitability of GH3B6 cells and TRH- and IP3-induced K+ conductance; 7) mesenchephalic dopaminergic neurons develop one type of K+ conductance in vivo but not in vitro; 8) cholecystokinin and IP3 facilitate depolarization-activated Ca2+ conductance in central neurons; 9) M1 and M3 muscarinic receptors and beta-adrenergic receptors expressed in fibroblasts transfected with the respective receptor genes mobilize Ca2+ from intracellular sites and activate K+ and Cl- conductances.